The present invention relates to nucleic acid molecules encoding hypusine mutants having the biological activity, of inhibiting cellular proliferation.
The present invention further relates to vectors comprising said nucleic acid molecules, to hosts transformed with said vectors, to methods of producing the polypeptide encoded by the nucleic acid molecule of the invention as well as to, the polypeptide itself. In addition, the present invention relates to pharmaceutical and diagnostic compositions comprising one or more of the aforementioned compounds, to methods for synchronizing an/or retarding cell growth and to the use of the vector of the invention in gene therapy.
The study of cell cycle has been one of the long standing interests of microbiologists and molecular biologists. Early work in molecular biology, for example, identified the myc-protein as one of the key regulators of cell division. Since this regulation of cell division might well have a crucial impact on processes generally known as neoplastic transformation, studies on cell cycle regulation naturally also have enjoyed a special interest in the medical field.
In order to more fully understanding cellular division, it is important to have a means at hand that interferes with, stops or synchronizes the cell cycle. In the past, a number of components that fulfill these requirements have been identified. Thus, temperature sensitive mutants such as cyclins, cdc 25 which at restrictive result in G2 arrest, chemotherapeutic agents like methotrexate or fluorouracil act as powerful inhibitors of DNA replication.
However, many of these compounds have an irreversible effect on the cell cycle. These as well as other compounds having similar properties are eventually toxic for the cells and accordingly of limited value, in particular with regard to pharmaceutical applicability.
The technical problem underlying the present invention was therefore to provide a means that can be conveniently employed in the study of cell cycle without having the adverse effects of the compounds known in the art. The solution to said technical problem is achieved by providing the embodiments characterized in the claims.
Accordingly, the present invention relates to a nucleic acid molecule encoding a polypeptide having the biological activity of inhibiting cellular proliferation selected from the group consisting of:
(a) nucleic acid molecules hybridizing to a complementary strand of a nucleic acid molecule comprising the nucleotide sequence shown in FIG. 5 (SEQ ID NO:1) or 6 (SEQ ID NO:3) and/or of a nucleic acid molecule coding for a polypeptide comprising the amino acid sequence shown in FIG. 5 (SEQ ID NO:2) or 6 (SEQ ID NO:4); and
(b) nucleic acid molecules, the nucleotide sequence of which is degenerate as a result of the genetic code to a nucleotide sequence of a nucleic acid molecule as defined in (a).